Hypoxia-Effects on Cai-Signaling and Ion Transport Activity of Lung Alveolar Epithelial Cells

Abstract

In excitatory cells specific responses upon changes in PO₂ are mediated by changes in intracellular Ca (Ca_i). We wanted to know whether ion transport of lung alveolar epithelial cells is regulated by Ca_i and whether Ca_i and Ca_i -signaling are affected by hypoxia in a way that might explain hypoxic transport inhibition (Mairbäurl et al. AJP 273: L797, 1997). The activity of transport (Na/K-pump, Na/K/2Cl-cotransport) was measured as unidirectional ⁸⁶Rb-uptake after A549 cells were exposed to hypoxia (3% O₂). Ca_i of primary cultured rat alveolar type II cells was measured by fura-2 epifluorescence. Depletion of Ca_i by extracellular chelators in presence of ionomycin or with thapsigargin as well as PKC inhibition decreases ⁸⁶Rb-uptake of normoxic and hypoxic A549 cells, whereas an increased Ca_i activates transport. Neither immediate nor prolonged exposure to hypoxia changes Ca_i significantly. The increase in Ca_i upon stimulation with ATP, which is caused mainly by release from intracellular stores, is smaller in hypoxia than in normoxia. These results indicate that ion transport of alveolar epithelial cells is modulated by Ca_i. A change in Ca_i does not mediate hypoxic transport inhibition. The decreased Ca_i transients in hypoxia might indicate a blunted response to extracellular stimuli.